Abstract The objective of Core A is to maintain a large collection of venoms and tissues from different Conus species and a library of purified venom peptides, synthetic peptides and their analogs. Biological materials will be collected mainly from various locations in the Phillipines. While the venom will be used as a direct source of purified peptides, tissues will be used as source of mRNA and genomic DNA for the molecular biological identification of toxins. Peptides will be identified both by biochemical purification and by molecular biological identification of peptide-encoding nucleic acid sequences. From a knowledge of the evolutionary relationship among the Conus species we will systematically analyze the venoms for specific ligands. Genetic markers for the cladististic analysis of Conideans will be obtained by PCR amplification of genomic DNA using specific primers. Complete toxin (pre-pro-mature toxin) sequences will be determined by identification of corresponding cDNAs from cDNA libraries constructed from venom-duct mRNA. PCR amplication of cDNA libraries with family-specific primers will also be used to determine the repertoire of expressed toxins. Molecular biological methods offer a means of identification of potential ligands (peptides) from very limited amounts of biological tissue. Conserved primers of different conotoxin superfamilies will be used to identify the respective toxins from genomic DNA by PCR amplification. The core will continue to provide synthetic peptides and venom samples to the scientific community. Over 100 laboratories were supplied during the previous funding period.